This proposal is orientated to test the hypothesis that nuclear morphology of mammalian sperm is determined by an intrinsic mechanism imparted by the formation of a DNA-protamine complex. The corollary to the hypothesis being that nuclear configuration is determined, in part, by specific interaction of cysteine residues between species specific protamine molecules present in the DNA-protamine complex. Species specificity and high cysteine content of protamines will be verified by comparison of results from amino acid analysis and electrophoresis of purified proteins isolated from different mammalian sperm. This study will be complemented by a biochemical analysis of the transition of protamines and non-histone proteins during spermiogenesis in the mouse. Separation of spermatids at different stages of condensation will be achieved by a combination of unit sedimentation and density gradient centrifugation. Nuclear proteins will be isolated from sperm and spermatid nuclei by extraction with guanidine hydrochloride and separation by gel electrophoresis. Chromosomal proteins will be distinguished by DNA-cellulose chromatography. A comparison of nuclear proteins isolated from different stages of spermatids from 'normal', 'quaking' and 'Win 18446-treated' mice will be undertaken to delineate nuclear proteins significant to nuclear morphology.